Subacute nicotine exposure in cultured cerebellar cells increased the release and uptake of glutamate

Cerebellar granule and glial cells prepared from 7 day-old rat pups were us ed to investigate the effects of sub-acute nicotine exposure on the glutama tergic nervous system. These cells were exposed to nicotine in various conc entrations for 2 to 10 days in situ. Nicotine-exposure did not result in an y changes in cerebellar granule and glial cell viability at concentrations of up to 500 muM. In cerebellar granule cells, the basal extracellular leve ls of glutamate, aspartate and glycine were enhanced in the nicotine-expose d granule cells. In addition, the responses of N-methyl-D-aspartate (NMDA)- induced glutamate release were enhanced at low NMDA concentrations in the n icotine-exposed granule cells. However, this decreased at higher NMDA conce ntrations. The glutaminase activity was increased after nicotine exposure. In cerebellar glial cells, glutamate uptake in the nicotine-exposed glial c ells were either increased at low nicotine exposure levels or decreased at higher levels. The inhibition of glutamate uptake by L-trans-pyrollidine-2, 4-dicarboxylic acid (PDC) was lower in glial cells exposed to 50 muM nicoti ne. Glutamine synthetase activity was lower in glial cells exposed to 100 o r 500 muM of nicotine. These results indicate that the properties of cerebe llar granule and glial cells may alter after subacute nicotine exposure. Fu rthermore, they suggest that nicotine exposure during development may modul ate glutamatergic nervous activity.